Project Summary With the ongoing opioid epidemic in the United States, alternative options for pain management are urgently needed. Data from recent ecological and open-label studies suggest that the introduction of medical cannabis laws are associated with decreased opioid prescribing and fewer overdose deaths, and that new initiations of cannabis are associated with prescription opioid discontinuations. With the rapid changes in the legal status of cannabis for medical and recreational purposes, more patients may be seeking cannabis for chronic pain management and its use as an analgesic is increasing in all age groups. However, the clinical outcomes of increased cannabis use for pain are unclear and there are calls for prospective empirical data. This proposal is for a prospective cohort study in a national sample of VA patients. The overall goal of this research is to improve our understanding of the extent to which cannabis use changes following prescription opioid discontinuation, and identify clinical outcomes associated with changes in cannabis use for pain. We will recruit 650 patients who are currently prescribed LTOT and have a past-month urine drug test result that is positive for cannabis/THC. Participants will complete a battery of self-report measures at baseline and every six months for two years. They will also complete monthly web-based assessments of cannabis use status and prescription opioid dose. A subset of participants who discontinue prescription opioids will complete qualitative interviews to better understand how cannabis use fluctuates following opioid discontinuation. The Specific Aims of this proposal are to characterize changes in cannabis use and symptoms of cannabis use disorder following prescription opioid dose discontinuation; evaluate associations between changes in opioid dose, cannabis use, and pain over time; and qualitatively explore patient-reported factors that lead to changes in cannabis use following prescription opioid discontinuation. The proposed research has broad implications for clinical care, providing novel data to examine how cannabis use changes following opioid dose modification, and the clinical impact of these changes. The overarching goal of this research is to generate empirical data to guide pain management approaches that optimize functional gains and decrease risk of adverse events.